Bone and soft tissue sarcomas are tumors that are related only by their origins from mesenchymal tissues. The present classification scheme for these tumors is based on the site of the tumor and the extent and type of cellular differentiation. Unfortunately, histopathologically identical tumors can differ greatly in clinical response. If the underlying genetic mechanisms of tumorigenesis in sarcomas were better known, distinguishing histologically similar but prognostically dissimilar tumors might be possible. Two recessive oncogenes, RB1 and p53, have been shown to undergo homozygous inactivation during tumorigenesis in many types of tumors, including bone and soft tissue sarcomas. The frequency of sarcomas that undergo these alterations is approximately 10-90% depending on the tumor type and possibly tumor stage, which suggests that in some sarcomas, these losses of gene function may be important in tumor progression rather than tumor initiation. In those sarcomas in which only a fraction of the tumors show a loss of expression of the RB1 and/or the p53 genes, this information may help in determining prognosis since it is likely that the loss of these genes represent changes in tumor stage that may not be histologically visible but may have tremendous importance in treatment outcome. This proposal is designed to use molecular genetic techniques to cor- relate loss of expression of the RB1 and p53 genes with clinical outcome in bone and soft-tissue sarcomas. A comprehensive genetic study of the correlation between tumor type and stage and the loss of the RB1 and/or p53 genes expression for all types of bone and soft tissue sarcomas will help to improve our understanding of the molecular events that take place during initiation and progression of these tumors. Such knowledge may be useful in producing a biologically relevant scheme for prognosis in sar- comas with a resultant improvement in the treatment of these diseases.